ABSTRACT
Background. Breakthrough infections post-COVID-19 vaccination increase with waning immunity and typically produce milder disease than infections in unvaccinated individuals. We investigated immuno-virologic responses and COVID-19 symptom burden upon breakthrough infection in participants from a Phase 3 study of 2-dose primary series AZD1222 vaccination (NCT04516746) to explore disease attenuation. Methods. Study participants who experienced protocol-defined COVID-19 symptoms initiated a series of illness visits over 28 days with collection of sera, nasopharyngeal (NP) swabs and saliva samples (SS), and documentation of symptoms (data-cut off: July 30, 2021). For baseline-seronegative participants with PCR-confirmed SARS-CoV-2 infection >=15 days after dose 2 of AZD1222 or placebo we assessed: anti-SARS-CoV-2 spike (S), nucleocapsid (N) and neutralizing antibody (Ab) titers by multiplex immunoassay and SARS-CoV-2 pseudovirus assay in sera;viral load by quantitative RT-PCR in NP swabs;and viral shedding by qualitative and quantitative RT-PCR in SS. Data were stratified by age and SARS-CoV-2 variant, and time since primary series dose 2. Results. Illness Day 1 (ILL-D1) S Ab GMTs in AZD1222 vaccinees were similar to peak GMTs seen 14 days after dose 2 of AZD1222 and were higher vs placebo at all timepoints. The magnitude of S Ab response differed by age: median GMTs were lower at ILL-D1 and higher at ILL-D14 in vaccinees aged >=65 vs 18-64 years (Fig.1). ILL-D1 overall, SARS-CoV-2 ancestral, alpha, and epsilon variant viral load titers in NP swabs were lower in vaccinees vs placebo (Fig 2). Mean viral load in NP swabs and viral shedding titers in SS were lower in vaccinees vs placebo at all timepoints. Vaccinees reported fewer COVID-19 symptoms than placebo participants, and experienced shorter symptom duration, particularly for fatigue and difficulty breathing. Figure 1. SARS-CoV-2 spike IgG antibody titers upon SARS-CoV-2 infection by participant age in AZD1222 vaccinees and placebo recipients during illness visits Figure 2. Quantification of viral load (nasopharyngeal swabs quantitative viral titer) by SARS- CoV-2 variant at Illness Visit Day 1 Conclusion. Improved S Ab responses, lower viral loads, and reduced symptom burden upon breakthrough infection in vaccinees vs placebo recipients, suggest that robust recall responses to AZD1222 vaccination may attenuate COVID-19 disease severity and duration. These findings alongside data on cellular immune responses to breakthrough infection will inform understanding of protective immunity to SARS-CoV-2 infection.
ABSTRACT
At the 2021 Conference on Retroviruses and Opportunistic Infections, there was a focus on progress toward hepatitis C virus (HCV) microelimination in geographic regions and targeted populations. HCV elimination is facilitated by well-tolerated, highly effective HCV treatment that requires essentially no on-treatment monitoring in most patients, as highlighted by the MINMON (Minimal Monitoring Study or A5360) study, and that should be increasingly available to children with new data supporting feasible treatment in younger patients. Challenges to HCV elimination include HCV reinfection via sexual exposure in men who have sex with men (MSM) and continued barriers to diagnosis and access to HCV treatment. Hepatitis B virus (HBV) suppression may take years in HIV/HBV-coinfected patients. This may have important consequences as the risk for hepatocellular carcinoma was associated in a dose-dependent manner with HBV viral load and was lowest in those with sustained undetectable HBV, highlighting the need for HBV DNA monitoring during therapy. Public health programs should prioritize improving hepatitis A and hepatitis B vaccination in at-risk populations, including people with HIV, as vaccinations rates for these preventable diseases continue to be suboptimal in many settings. Fatty liver disease, heavy alcohol use, antiretroviral therapy, and COVID-19 infection were also examined as drivers of hepatic disease in HIV infection.